Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia.
Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia.
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DOI：
10.1016/b978-0-323-91534-2.00009-6
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发表时间：
2022
影响因子：
--
通讯作者：
Nanduri, Jayasri
中科院分区：
文献类型：
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作者：
Prabhakar, Nanduri R;Peng, Ying-Jie;Nanduri, Jayasri
本章回顾了在高海拔地区对慢性缺氧（CH）的心肺适应，以及慢性间歇性缺氧（CIH）引起的阻塞性睡眠呼吸暂停（OSA）引起的心肺病理。短期CH通过颈动脉体（CB）化学反射增加呼吸（对缺氧的适应性适应）和血压（BP）。血管球细胞增生，离子通道改变，和募集额外的兴奋性分子与CH引起的CB化学反射增强有关。缺氧诱导因子的转录激活低氧诱导因子（HIF-1和HIF-2）是呼吸系统对短期CH适应的主要分子机制，高原人长期CH后，低氧诱导反应（HVR）减弱由于CB对缺氧的反应脱敏和中枢神经系统对CB感觉信息的处理受损而降低了血压。由长期CH引起的通气变化在返回海平面后不易逆转。OSA患者和啮齿类动物CIH表现出CB化学反射增强，低氧性呼吸反应增加和高血压。活性氧（ROS）的产生增加是CIH诱导的CB化学反射增强和随后的心肺病理学的主要细胞机制。CIH引起的ROS生成是由非转录的、破坏的HIF-1和HIF-2依赖性转录以及表观遗传机制介导的。
This chapter reviews cardiorespiratory adaptations to chronic hypoxia (CH) experienced at high altitude and cardiorespiratory pathologies elicited by chronic intermittent hypoxia (CIH) occurring with obstructive sleep apnea (OSA). Short-term CH increases breathing (ventilatory acclimatization to hypoxia) and blood pressure (BP) through carotid body (CB) chemo reflex. Hyperplasia of glomus cells, alterations in ion channels, and recruitment of additional excitatory molecules are implicated in the heightened CB chemo reflex by CH. Transcriptional activation of hypoxia-inducible factors (HIF-1 and 2) is a major molecular mechanism underlying respiratory adaptations to short-term CH. High-altitude natives experiencing long-term CH exhibit blunted hypoxic ventilatory response (HVR) and reduced BP due to desensitization of CB response to hypoxia and impaired processing of CB sensory information at the central nervous system. Ventilatory changes evoked by long-term CH are not readily reversed after return to sea level. OSA patients and rodents subjected to CIH exhibit heightened CB chemo reflex, increased hypoxic ventilatory response, and hypertension. Increased generation of reactive oxygen species (ROS) is a major cellular mechanism underlying CIH-induced enhanced CB chemo reflex and the ensuing cardiorespiratory pathologies. ROS generation by CIH is mediated by nontranscriptional, disrupted HIF-1 and HIF-2-dependent transcriptions as well as epigenetic mechanisms.